The Herbal Medicine Extract Rutin Reduces Beta Amyloid‐induced Depolarization of Glutamatergic Neurons

Abstract

Currently, two of the major clinical hallmarks of Alzheimer’s disease (AD) are senile plaques formed by beta‐amyloid (Aβ) deposits and neurofibrillary tangles caused by tau protein hyperphosphorylation. Extracellular Aβ accumulation could cause neuronal death and this eventually leads to the individual developing cognitive deficits and memory impairment. Aβ accumulation seems to mediate an increase of glutamate concentration by which excess glutamates bind NMDA receptors and/or AMPA receptors at the synaptic and/or extrasynaptic cleft manner and subsequently trigger excitotoxicity. Memantine, the only clinical drug on the basis of synthetic NMDA receptor antagonist, developed to treat mild to severe AD patients. Therefore, we aim to develop more new drugs which could alleviate the Aβ‐induced pathophysiology. We previously established a drug screening model that employed glutamatergic neurons that were cultivated from mouse brain cortex with the help of bis‐(1,3‐dibutylbarbituric acid)‐trimethine oxonol (DiBAC4(3)), a fluorescent dye able to sense depolarization. We found rutin, a pure compound extracted from Ginkgo biloba, is able to attenuate Aβ‐induced abnormal depolarization in these glutamatergic neurons. Utilizing receptor agonists, we revealed that rutin mediates the inhibition of NMDA receptor, but not AMPA receptor to exert such an effect. Next the molecular mechanism(s) behind rutin and Aβ‐induced abnormal depolarization, as well as various other parameters such as electrophysiology, are at present under investigation. Our findings, when taken together, clearly show that the pure compound rutin is able to reduce Aβ‐induced depolarization of these neurons. Although research exploring the detail mechanisms of rutin is ongoing, this drug may have important benefits and great potential with respect to AD therapy.